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981.
Using pharmacological means we investigated the functional interactions between the estrogen receptor (ER)-, protein kinase A (PKA)-, and mitogen-activating protein kinase (MAPK)-mediated pathways in the regulation of lactotroph proliferation in primary culture. Treatment of lactotrophs for 28 h with the PKA inhibitor H89 or KT5720, an effective inhibitor of forskolin-induced proliferation, inhibited both insulin- and estradiol-induced proliferation. Inhibition of the MAPK activity by PD98059 or U0126 suppressed not only insulin-induced proliferation but also forskolin- and estradiol-induced proliferation. However, treatment for 28 h with the antiestrogens 4-hydroxy tamoxifen and ICI182780 failed to antagonize estradiol-induced lactotroph proliferation but instead enhanced it. Prolonging the antiestrogen treatment time from 28 to 88 h was effective in antagonizing estradiol-induced proliferation with this long-term treatment also inhibiting insulin- and forskolin-induced proliferation. There was no decrease in these mitogen-induced proliferations following treatment with a progesterone antagonist or protein kinase C inhibitor. These results suggest that cross-talk occurs between the ER-, PKA-, and MAPK-mediated signaling pathways in the regulation of lactotroph proliferation, and that antiestrogens stimulate and inhibit estradiol-induced proliferation in a time-dependent manner. 相似文献
982.
Ou J Fontana JT Ou Z Jones DW Ackerman AW Oldham KT Yu J Sessa WC Pritchard KA 《American journal of physiology. Heart and circulatory physiology》2004,286(2):H561-H569
An increase in the association of heat shock protein 90 (HSP90) with endothelial nitric oxide (NO) synthase (eNOS) is well recognized for increasing NO (NO*) production. Despite the progress in this field, the mechanisms by which HSP90 modulates eNOS remain unclear due, in part, to the fact that geldanamycin (GA) redox cycles to generate superoxide anion (O(2)(-*) and the fact that inhibiting HSP90 with GA or radicicol (RAD) destabilizes tyrosine kinases that rely on the chaperone for maturation. In this report, we determine the extent to which these side effects alter vascular and endothelial cell function in physiologically relevant systems and in cultured endothelial cells. Vascular endothelial growth factor (VEGF)-stimulated vascular permeability, as measured by Evans blue leakage in the ears of male Swiss mice in vivo, and acetylcholine-induced vasodilation of isolated, pressurized mandibular arterioles from male C57BL6 mice ex vivo were attenuated by N(omega)-nitro-L-arginine methyl ester (L-NAME), GA, and RAD. Z-1[N-(2-aminoethyl)-N-(2-ammonoethyl)amino]diazen-1-ium-1,2-dioate (DETA-NONOate), a slow releasing NO. donor, increased vasodilation of arterioles pretreated with GA, RAD, and L-NAME equally well except at 10(-5) M, the highest concentration used, where vasodilation was greater in pressurized arterioles treated with L-NAME than in arterioles pretreated with GA or RAD alone. Both GA and RAD reduced NO* release from stimulated endothelial cell cultures and increased O(2)(-*) production in the endothelium of isolated aortas by an L-NAME-inhibitable mechanism. Pretreatment with RAD increased stimulated O(2)(-*) production from eNOS, whereas pretreatment with genistein (GE), a broad-spectrum tyrosine kinase inhibitor, did not; however, pretreatment with GE + RAD resulted in a super-induced state of uncoupled eNOS activity upon stimulation. These data suggest that the tyrosine kinases, either directly or indirectly, and HSP90-dependent signaling pathways act in concert to suppress uncoupled eNOS activity. 相似文献
983.
Stable isotope labeling of Arabidopsis thaliana for an NMR-based metabolomics approach 总被引:5,自引:0,他引:5
Nuclear magnetic resonance (NMR) will become a key technology in plant metabolomics with the use of stable isotope labeling and advanced hetero-nuclear NMR methodologies. To demonstrate the power of this approach, we performed multi-dimensional hetero-nuclear NMR analysis of metabolic movement of carbon and nitrogen nuclei in Arabidopsis thaliana. First, distinct ethanol-stress response was investigated using (13)C-labeled wild type and an ethanol-hypersensitive mutant plants. Furthermore, we followed nitrogen fluxes in (15)N-labeled seeds during the initiation of germination in vivo. The future role of stable isotope-labeling combined with advanced hetero-nuclear NMR in plant metabolomics is discussed. 相似文献
984.
Guan J Wan XS Zhou Z Ware J Donahue JJ Biaglow JE Kennedy AR 《Radiation research》2004,162(5):572-579
Of particular concern for the health of astronauts during space travel is radiation from protons and high-mass, high-atomic-number (Z), and high-energy particles (HZE particles). Space radiation is known to induce oxidative stress in astronauts after extended space flight. In the present study, the total antioxidant status was used as a biomarker to evaluate oxidative stress induced by gamma rays, protons and HZE-particle radiation. The results demonstrate that the plasma level of total antioxidants in Sprague-Dawley rats was significantly decreased (P < 0.01) in a dose-dependent manner within 4 h after exposure to gamma rays. Exposure to protons and HZE-particle radiation also significantly decreased the serum or plasma level of total antioxidants in the irradiated animals. Diet supplementation with L-selenomethionine alone or a combination of selected antioxidant agents was shown to partially or completely prevent the decrease in the serum or plasma levels of total antioxidants in animals exposed to gamma rays, protons or HZE particles. These findings suggest that exposure to space radiation may compromise the capacity of the host antioxidant defense and that this adverse biological effect can be prevented at least partially by dietary supplementation with L-selenomethionine and antioxidants. 相似文献
985.
Five new C21 steroidal glycosides, namely, komarosides D (1), E (2), F (3), G (4), and H (5), along with two known C21 steroidal glycosides cynatratoside E (6) and hancoside A (7), were isolated from the ethanol extract of the roots of Cynanchum komarovii Al.Iljinski (Asclepiadaceae). Their structures were determined by physiochemical and spectroscopic analysis. Among these glycosides, five had an aberrant 13,14:14,15-disecopregnane-type skeleton, and the other two had normal four-ring C21 steroid skeletons. The existence of more than one type of C21 steroid skeleton in one species is rare in the plants of the family Asclepiadaceae, and this has chemotaxonomic significance for this species. 相似文献
986.
Liu P Zhu J Lu Y 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》2004,109(2):370-376
Computer simulations were used to study the efficiency of MAS for breeding self-fertilizing crops, based on a general model including additive, dominance and epistasis. It was shown that MAS not only gave larger genetic responses but also dramatically increased the frequencies of superior genotypes as compared with phenotypic selection. However, the advantages of MAS over phenotypic selection were considerably reduced when conducting selection in later generations. A modified method combining MAS in early generations with phenotypic selection in later generations was thus proposed from an efficiency standpoint. We also proposed a potential index to measure the probability of an individual showing superior genotypes under selfing. It was apparent that more superior genotypes could be derived from selection by using the potential index than by using other methods. The implications of these findings for plant breeding are discussed.Communicated by H.C. Becker 相似文献
987.
Do highly trained monkeys walk like humans? A kinematic study of bipedal locomotion in bipedally trained Japanese macaques 总被引:2,自引:0,他引:2
Hirasaki E Ogihara N Hamada Y Kumakura H Nakatsukasa M 《Journal of human evolution》2004,46(6):739-750
In this study, we examined the kinematics of bipedal walking in macaque monkeys that have been highly trained to stand and walk bipedally, and compared them to the kinematics of bipedal walking in ordinary macaques. The results revealed that the trained macaques walked with longer and less frequent strides than ordinary subjects. In addition, they appear to have used inverted pendulum mechanics during bipedal walking, which resulted in an efficient exchange of potential and kinetic energy. These gait characteristics resulted from the relatively more extended hindlimb joints of the trained macaques. By contrast, the body of the ordinary macaques translated downward during the single-limb stance phase due to more flexed hindlimb joints. This resulted in almost in-phase fluctuations of potential and kinetic energy, which indicated that energy transformation was less efficient in the ordinary macaques. The findings provide two insights into the early stage of the evolution of human bipedalism. First, the finding that training considerably improved bipedal walking a posteriori may explain why the very first bipeds that might not yet have been morphologically adapted to bipedal walking continued to walk bipedally. The evolutionary transition from quadrupedalism to bipedalism might not be as difficult as has been envisioned. In addition, the finding that macaques, which are phylogenetically distant from humans and in which bipedal walking is unlike human walking, could develop humanlike gait characteristics with training, provides strong support for the commonly held but unproven idea that the characteristics of the human gait are advantageous to human bipedalism. 相似文献
988.
The CCL4 chemokine is secreted by a variety of cells following stimulation. CCL4 affects several different types of cells that are important for acute inflammatory responses and are critical for the development of specific immune responses to foreign antigens. The human genome contains two genes for the CCL4 chemokine. Although highly homologous, the two genes encode slightly different proteins. We analyzed the mRNA expressed in monocytes and B lymphocytes and found that while monocytes express predominantly one CCL4 gene, known as ACT-2, peripheral blood B lymphocytes express a mixture of ACT-2 and the second CCL4 gene, lymphocyte activating gene-1 (LAG-1). Although peripheral blood B cells, CD27– B cells, and CD27+ B cells all express a mixture of LAG-1 and ACT-2, the B-cell lines that were studied regulate the two genes independently. RL, SU-DHL-6, and REH cells predominantly express LAG-1. These studies demonstrate that monocytes and B cells utilize different mechanisms to regulate expression of the two CCL4 genes and suggest that the two genes may not have identical activities. 相似文献
989.
Two morphological types of appendages, an anchor-like appendage and a peritrichate fibril-type appendage, have been observed on cells of an adhesive bacterium, Acinetobacter sp. strain Tol 5, by use of recently developed electron microscopic techniques. The anchor extends straight to the substratum without branching and tethers the cell body at its end at distances of several hundred nanometers, whereas the peritrichate fibril attaches to the substratum in multiple places, fixing the cell at much shorter distances. 相似文献
990.
Four trans-planaramineplatinum(II) complexes code named YH9, YH10, YH11 and YH12 each of the form trans-PtL(NH(3))Cl(2), where L=2-hydroxypyridine and 3-hydroxypyridine, imidazole, and imidazo(1,2-alpha)pyridine for YH9, YH10, YH11 and YH12, respectively, have been synthesized and the activity of the compounds against human cancer cell lines, cell uptake, DNA-binding and nature of interaction with pBR322 plasmid DNA have been studied. The compound having imidazo(1,2-alpha)pyridine ligand as one the carrier ligands in the trans-configuration is found to be significantly more active than cis-platin against ovarian A2780(cisR) cancer cell line corresponding with higher Pt-DNA binding. All other compounds have resistance factors less than that for cis-platin in the A2780 and A2780(cisR) cell lines. A greater prevention of BamH1 digestion with increasing concentration of the compounds indicates that as the compounds bind with nucleobases in DNA, the DNA conformation is changed sufficiently so as to prevent BamH1 digestion at the specific GG site. Gel electrophoresis results also indicate that as the compounds bind to DNA, unwinding of supercoiled form I DNA takes place to change it from the negatively supercoiled form I through relaxed circular form I to the positively supercoiled form I. 相似文献